biostudies-literatureValledor MNICHD NIH HHSNIA NIH HHSNational Institutes of HealthNIGMS NIH HHS112686https://www.ebi.ac.uk/biostudies/studies/S-EPMC10461597biostudies-literatureUnknown42(7)XIST RNA triggers chromosome-wide gene silencing and condenses an active chromosome into a Barr body. Here, we use inducible human XIST to examine early steps in the process, showing that XIST modifies cytoarchitecture before widespread gene silencing. In just 2-4 h, barely visible transcripts populate the large "sparse zone" surrounding the smaller "dense zone"; importantly, density zones exhibit different chromatin impacts. Sparse transcripts immediately trigger immunofluorescence for H2AK119ub and CIZ1, a matrix protein. H3K27me3 appears hours later in the dense zone, which enlarges with chromosome condensation. Genes examined are silenced after compaction of the RNA/DNA territory. Insights into this come from the findings that the A-repeat alone can silence genes and rapidly, but only Cell reportsEarly chromosome condensation by XIST builds A-repeat RNA density that facilitates gene silencing.PMC10461597R01 HD094788R01HD091357R01 HD091357F32 AG056131R35 GM122597R35GM122597R01HD094788F32 AG056131-01Carone DMValledor MByron MLawrence JBDumas BHall LLfalseEarly chromosome condensation by XIST builds A-repeat RNA density that facilitates gene silencing.XIST RNA triggers chromosome-wide gene silencing and condenses an active chromosome into a Barr body. Here, we use inducible human XIST to examine early steps in the process, showing that XIST modifies cytoarchitecture before widespread gene silencing. In just 2-4 h, barely visible transcripts populate the large "sparse zone" surrounding the smaller "dense zone"; importantly, density zones exhibit different chromatin impacts. Sparse transcripts immediately trigger immunofluorescence for H2AK119ub and CIZ1, a matrix protein. H3K27me3 appears hours later in the dense zone, which enlarges with chromosome condensation. Genes examined are silenced after compaction of the RNA/DNA territory. Insights into this come from the findings that the A-repeat alone can silence genes and rapidly, but only 2023-01-01T00:00:00Z2023 Jul2026-04-29T02:20:55.634Z2025-02-19T04:01:40.758ZS-EPMC104615973738452710.1016/j.celrep.2023.112686